The study is assembling a well-characterized cohort of patients with presumed chronic Lyme disease and relevant controls. These patients are being extensively evaluated in a cross-sectional study and the neuroborreliosis patients will be followed prospectively after therapy with intravenous ceftriaxone. These studies will yield a prospective database upon which stringent diagnostic criteria can be established and future therapeutic trials can be designed. At this point, 32 patients and controls have been enrolled in the study. This study is in its early phase of development, and, at this point, it is too early to draw conclusions from the analysis of the results of the multiple and extensive testing done in the enrolled patients. Multiple research projects are being developed based on the findings in this population. All of these projects are ongoing. In collaboration with Dr. Stephen Fischer and Dr. Susan Weir from the Clinical Pathology Department at the Warren Grant Magnuson Clinical Center, a new PCR assay for Borrelia has been developed and is now in early phase of clinical application. The PCR is being used to seek for the presence of Borrelia in frozen brain biopsies from patients with Alzheimer?s disease and matched controls. This is being performed in collaboration with Dr. Juan Troncoso from JHU, who provided the brain biopsies. In collaboration with Dr. Roland Martin and Dr. Henry McFarland from NINDS, Borrelia-specific T cell clones have been isolated from peripheral blood, joint and/or cerebrospinal fluid from patients with chronic neuroborreliosis and Lyme arthritis. The cytokine profiles of some of these clones have been studied. Also, one clone has been studied using combinatorial peptide libraries for fine definition of the reactive peptide. In collaboration with Dr. Grafman from NINDS, we are studying the neuropsychological findings of patients suffering from chronic Lyme disease and controls. In collaboration with Dr. Choo and Dr. Lawrence Shotland from NIDCD, we are studying the audiological findings in patients with chronic Lyme disease. In collaboration with Dr. Duray from NCI and with Dr. Leonid Margolis from NICHD, we are developing a new system for cultivation of Borrelia in vitro . This system may enable the culture of Borrelia in an environment that is most closely related to the different environments that Borrelia encounters in the human host. These will be important in the understanding of the pathogenesis of infection in vivo.